Central 5-hydroxytryptamine receptor-linked protein kinase C translocation: a functional postsynaptic signal transduction system.
The effect of 5-hydroxytryptamine (5-HT) receptor stimulation on protein kinase C (PKC) activity and translocation was assessed in slices or synaptosomes obtained from rat brain. Serotonin (0.5-100 microM) and the specific 5-HT2 receptor agonist 1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane (DOI) (0.01-10 microM) but not the 5-HT1A or 5-HT1B agonists elicited time- and dose-related translocations in cortical slices. The maximal translocation elicited by 5-HT (10-100 microM, 15 min) or DOI (1 microM, 10 min) was similar to that achievable by the phorbol ester phorbol myristate acetate (PMA) (162 nM). In synaptosomes, short exposures to depolarizing concentrations of K+ (45-65 mM) resulted in PKC translocation. In addition, PMA but not serotonin induced enzyme translocation in synaptosomes. In slices, serotonin-stimulated PKC translocation was prevented by 5-HT2 antagonists but not by dopamine or alpha-adrenergic antagonists. PKC translocation induced by serotonin but not by PMA was inhibited by incubation of slices in a Ca2+-free medium. However, addition of 0.5 mM ethylene glycol bis(beta-aminoethyl ether)-N,N,N',N'-tetraacetic acid to the incubation mixture abolished the effects of both serotonin and PMA. These results indicate that, in cortical slices, serotonin operating via a 5-HT2 postsynaptic receptor can induce the translocation of PKC from cytosol to membrane. This action of the neurotransmitter appears to be dependent on extracellular Ca2+.
Wang
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Department of Psychiatry, Medical College of Pennsylvania, Philadelphia 19129.
Friedman
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D000818:Animals; D001921:Brain / Q000502:physiology*; D002118:Calcium / Q000502:physiology; D002451:Cell Compartmentation; D002462:Cell Membrane / Q000378:metabolism; D002540:Cerebral Cortex / Q000201:enzymology; D003342:Corpus Striatum / Q000201:enzymology; D003600:Cytosol / Q000378:metabolism; D006624:Hippocampus / Q000201:enzymology; D066298:In Vitro Techniques; D011493:Protein Kinase C / Q000378:metabolism*; D051381:Rats; D011985:Receptors, Serotonin / Q000502:physiology*; D012701:Serotonin / Q000494:pharmacology*; D012702:Serotonin Antagonists / Q000494:pharmacology; D015398:Signal Transduction
D011985:Receptors, Serotonin; D012702:Serotonin Antagonists; D012701:Serotonin; D011493:Protein Kinase C; D002118:Calcium